This study is an investiation of the regulation of the pulmonary circulation by hypoxia, hypercapnia and other humoral and pharmacologic agents, such as histamine and serotonin, in the normal situation and in disease. It is designed to elucidate the mechanisms whereby these gaseous and humoral agents produce pulmonary hypertension, such as is observed in patients with chronic lung disease and cor pulmonale and in individuals at high altitude, and to study the effect of lack of this mechanism in patients who may possibly have non-reactive pulmonary vasculature, such as those with familial dysautonomia. The techniques involve animal and in-vitro methods to assess both the role of the pulmonary perivascular mast cell as a chemoreceptor releasing vasoactive materials, and the physiology and pharmacology of the alpha and beta adrenergic system, which may make the pulmonary circulation, in contrast to the systemic one, uniquely sensitive to these vasoactive substances. Computer modeling techniques of the pulmonary circulation and studies of the distribution of pulmonary blood flow in patients who may lack the characteristic pulmonary pressor response to hypoxia will also be utilized.